Team West Pharmaceutical Services December 12, 2012

1 PhaseDeliverables 1 Definition of Customers and their Needs/Wants/Constraints Project Scope definition refinement Identification of science and technology relevant to project Identification of key performance and cost metrics Initial benchmarking results 2 Conceptual design to satisfy sponsor’s requirements Design specifications necessary to purchase components, manufacture, and assemble the proof-of-concept prototype Project cost 3 Conceptual design to satisfy sponsor’s requirements Design details for solution to sponsor’s project Updated Project Plan with allocation of needed resources Updated test plan that is based on a credible set of experiments and uses valid measurement methodologies 4 A viable prototype A transition plan that facilitates the implementation of the project results into the sponsor’s business

2 PhaseDeliverables 1 Definition of Customers and their Needs/Wants/Constraints Project Scope definition refinement Identification of science and technology relevant to project Identification of key performance and cost metrics Initial benchmarking results 2 Conceptual design to satisfy sponsor’s requirements Design specifications necessary to purchase components, manufacture, and assemble the proof-of-concept prototype Project cost 3 Conceptual design to satisfy sponsor’s requirements Design details for solution to sponsor’s project Updated Project Plan with allocation of needed resources Updated test plan that is based on a credible set of experiments and uses valid measurement methodologies 4 A viable prototype A transition plan that facilitates the implementation of the project results into the sponsor’s business

Background 3 West Pharmaceutical Services is a manufacturer of pharmaceutical packaging and injectable drug delivery system components for pharmaceutical and medical device companies RU packaging systems must have at least 3 removable packaging bags to comply with West RU packaging standards Ready to use (RU) products have multiple layers of packaging and packaging is shed as it goes through clean rooms prior to use Products are sterilized, packaged, and are ready to be used without any further preparations

Current Design - Westar RU for Lyo Stoppers 3 layers –Foil (Tertiary) –PE, Tyvek (Secondary) –PE, Tyvek (Primary) Primary and secondary bags are autoclaved Packaging integrity risks with removing the secondary bag Poor ergonomics 4 Figure 1: Current primary bag

To develop an innovative, sterile packaging system that adds value to West’s products and improves customer handling. Project Scope

Prioritized Sponsor Wants 1 Compatible with steam sterilization (minimum of 122 ℃ for 60 minutes) 2Maintain package integrity 3 Durability compared to current packaging: meet ASTM F390 standards for Gelbo testing 4Meet minimum shelf-life requirements 5Multiple layers that are able to be shed 6Easy to handle 7 Easy access to package contents without compromising packaging integrity 8Visibility of Package Contents 9Maintain cost to manufacture 10Aesthetic

WantTarget Value (s) Compatible with steam sterilization (minimum of 122 ℃ for 60 minutes) Yes Maintain package integrityMeets all applicable ASTM standards Durability compared to current packaging: meet ASTM F390 standards for Gelbo testing 900 strokes with < 7 pinholes Meet minimum shelf-life requirements6 months Multiple layers that are able to be shed> 3 layers Easy to handle<15 lbs-25 lbs Easy access to package contents without compromising packaging integrity Time to remove 1 layer: < 15 seconds Maintain cost to manufacture$6-$10 Aesthetic 80% of test subjects respond ‘Yes’ to improvement over current design Verify Contents of ContainerVisible from outer bag: Yes/No Metrics

3 Major Categories were considered for Concept Generation Sealing / Access Methods # / Type of Bags Rigid / Non- Rigid 8

Non-Rigid Concepts 9 3-Layers composed of PE / Tyvek. Heat-sealed. Ripcord opening method. 3-Layers composed of PE / Tyvek. Handles on each layer. Heat-sealed.

Updated Sponsor Wants 1 Compatible with steam sterilization (minimum of 122 ℃ for 60 minutes) 2Maintain integrity 2.5Rigid 3 Durability compared to current packaging: meet ASTM F390 standards for Gelbo testing 4Meet minimum shelf-life requirements 5Multiple layers that are able to be shed 6Easy to handle 7 Easy access to package contents without compromising packaging integrity 8Visibility of Package Contents 9Maintain cost to manufacture 10Aesthetic

3 Variations of Rigid Containers were Considered 11 Rigid Multiple Rigid Containers Rigid Primary Container Rigid Tertiary Container

12 Rigid Multiple Rigid Containers Not cost-plausible Rigid Tertiary Container Rigid Primary Container

13 Rigid Multiple Rigid Containers Not cost-plausible Rigid Tertiary Container Rigid Primary Container

Rigid Tertiary Container 14 Outer container – Rigid PE/Tyvek Primary and secondary deformable PE/Tyvek bags inside

15 Rigid Multiple Rigid Containers Not cost-plausible Rigid Tertiary Container Sponsor Veto Rigid Primary Container

16 Rigid Multiple Rigid Containers Not cost-plausible Rigid Tertiary Container Sponsor Veto Rigid Primary Container

17 Initial Rigid Primary Container Concepts Figure 1: RipcordFigure 2: Access Hole Figure 3: Peel-able Heat Seal

18 Selected Model for Prototype: Primary Container

Final Prototype 19 Figure 4. Final primary container design. Heat-sealed Tyvek® 1073B with 24AL Xhale® adhesive top Makrolon GP Polycarbonate rigid container Prototype container can hold roughly 4,500 Lyo stoppers

Final Prototype 20 Figure 5. Final packaging system featuring 2 removable layers around a rigid primary container. Primary container surrounded by Tyvek/Polyethylene secondary bag Secondary bag surrounded by a Nylon/Polyethylene tertiary bag Secondary bag vacuum-sealed around primary container to conform outer bags to primary container for improved ergonomics

Budget Breakdown 21 TOTAL BUDGET: $10,000 Test Materials$400 Manufacturing Cost$3,500 Initial Fees$1,500 TOTAL COST$5,400

Testing Preliminary Tests: (6) 1”x11” Polycarbonate samples –Tension –Peel –Material Integrity Final Testing: Final prototype –Stacking –Material Integrity –Peel 22

Testing Preliminary Tests: (6) Polycarbonate samples per test –Tension –Peel –Material Integrity Final Testing: Final prototype –Stacking –Material Integrity –Peel 23

Tension Testing of Polycarbonate Specimens 24 Prepare Specimen to height and thickness dimensions of final container with arbitrary width. Reduce load displacement data to obtain stress and strain information. Extrapolate stress results to determine maximum stacking load of the final container. After the required autoclave cycle, strength increased by ~10%

Tyvek / Polycarbonate Interface Peel Strength Test 25 Prepare Specimens of Polycarbonate and Tyvek to equal but arbitrary dimensions. Bond Tyvek to Polycarbonate as instructed by PacTech. Measure force to separate Tyvek layer from polycarbonate with instron testing machine. Determine strength to peel based on area of sealant. Minimum Peel Strength was determined to be 3.3lbf/in

Steam Autoclave Material Integrity Test 26 Prepare Specimen to arbitrary dimensions. Measure Dimensions of Specimen with caliper. Place specimen in autoclave and run at specified cycle. After run is complete, measure sample and document and changes. Vary orientation of specimens in autoclave. No relevant change in geometry due to the required autoclave cycle

Testing Preliminary Tests: (6) 1”x11” Polycarbonate samples –Tension –Peel –Material Integrity Final Testing: Final prototype –Stacking –Material Integrity –Peel 27

Stacking Test 28 Stacking tests resulted in a maximum stacking load of 110 lbf

Material Integrity Test – Steam Autoclave Still to be performed 29

Thermoform vs. Injection Molding 30 Example quote from Advanced Plastics, NY AttributeThermoformInjection Mold Mold fabrication time4-6 weeks18-24 weeks Parts per year (per mold) Up to 100,000 Cost of mold$ 3,000$ 22,000 Thermoform was best choice for a rapid prototype with reduced prototyping costs Costs would have been ~7x more and not been delivered until mid- February For actual production of larger unit numbers, injection molding is obvious choice.

Path Forward On production of >10,000 parts, Injection Molding is recommended as process choice. –Faster production time –Cheaper per part cost –Less downtime as mold lasts for more cycles. Opinion of group that trays were thicker than needed, future optimization of dimensions would drive materials cost down. 31 *Model used to produce costs assumed 2.00$ / lb material (medium engineering grade). Actual research shows an expected 1.60$ / lb Polycarbonate. Estimated costs (using Injection Molding calculator from University of Massachusetts) shown below in table. Based on empirical data.

Path Forward (Testing Next Steps) 32 Samples Processed and Subjected to Simulated Distribution Conditioning Run autoclave sterility cycle per current procedure Visually inspect seals for gross defects per ASTM F1886. Subject filled cartons to simulated distribution conditioning per ASTM , Distribution Cycle 2 (single parcel).  Schedule A Manual Handling-First Sequence Set  Schedule B Vehicle Stacking-Compression  Schedule F Loose Load Vibration, Method A1- Truck 40 min  Schedule E Vehicle Vibration- Truck 30 minutes, Air 120 minutes, Truck 30 minutes (column stacked)  Schedule A Manual Handling- Second Sequence Set  Schedule I Low Pressure ft f0r 60 minutes Perform integrity testing on package system:  Visually inspect seals for gross defects per ASTM F1886.  If there are any questionable seals, use methylene blue dye penetration to confirm seal quality (per ASTM 1929)  Perform integrity testing via vacuum decay testing (ASTM F2338) or other suggested method.

Acknowledgments West Team Mark Launer Tim Miller Monica Habash Pactech Frank Colombo Chad Buchta 33 UD Dr. Buckley Jim Farmer Center for Composite Materials

Questions? 34